Polydrug use refers to the use of two or more psychoactive drugs in combination to achieve a particular effect. In many cases one drug is used as a base or primary drug, with additional drugs to leaven or compensate for the side effects of the primary drug and make the experience more enjoyable with drug synergy effects, or to supplement for primary drug when supply is low.[1]

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Polydrug use often carries with it more risk than use of a single drug, due to an increase in side effects, and drug synergy. The potentiating effect of one drug on another is sometimes considerable and here the licit drugs and medicines – such as alcohol, nicotine and antidepressants – have to be considered in conjunction with the controlled psychoactive substances. The risk level will depend on the dosage level of both substances. Concerns exist about a number of pharmacological pairings: alcohol and cocaine increase cardiovascular toxicity; alcohol or depressant drugs, when taken with opioids, lead to an increased risk of overdose; and opioids or cocaine taken with ecstasy or amphetamines also result in additional acute toxicity.[2]Benzodiazepines are notorious for causing death when mixed with other CNS depressants such as opioids, alcohol, or barbiturates.[3][4][5]

Within the general concept of multiple drug use, several specific meanings of the term must be considered. At one extreme is planned use, where the effects of more than one drug are taken for a desired effect. Another type is when other drugs are used to counteract the negative side effects of a different drug (e.g. depressants are used to counteract anxiety and restlessness from taking stimulants). On the other hand, the use of several substances in an intensive and chaotic way, simultaneously or consecutively, in many cases each drug substituting for another according to availability.[2]

A study among treatment admissions found that it is more common for younger people to report polydrug drug use.[7]

MDMA taken in combination with or the day after low doses of viagra (20mg) has been shown to reduce MDMA-induced serotonin deficit in rats by increasing resistance to MDMA-induced oxidative stress.[8][9]